Patients with systemic lupus erythematosus (SLE) appear to have an increased susceptibility to infections caused by pyogenic microorganisms. In order to determine the pathogenesis of this major cause of morbidity and mortality, the applicant proposes to examine the functions in vitro of two major components of host defenses in patients with SLE: polymorphonuclear leukocytes (PMN) and the complement system. Specific attention will be directed at cellular and humoral aspects of chemotaxis. The applicant will examine in detail the nature, mechanism of action, and significance of a uniquely specific, reversible inhibitor of complement (C5)-derived chemotactic activity found in serum from approximately one-third of patients with SLE. Preliminary studies of patients with SLE, which suggest that the presence of this inhibitor may contribute (in part) to an increased susceptibility to severe bacterial infections, will be expanded. Abnormal functions of PMN and complement in patients with SLE will be related to disease activity, history of infection, therapy, and several serologic parameters (e.g., antimuclear antibodies, complement levels, antibodies to native DNA, etc.). The applicant will also examine the nature and mechanism of action of a previously undescribed anionic polypeptide ("helper factor") which regulates the expression of C5-derived chemotactic activity in serum and which appears to be the "target" of the SLE inhibitor. These studies should provide important new information regarding host defense mechanisms in patients with SLE. They may not only explain why these patients have an increased susceptibility to infection, but also may provide clues for more rational forms of therapy. On a more basic level, these studies should yield new information that is fundamental for our understanding of mechanisms involved in regulating the biological activity of complement-derived peptides.